Neurological diseases and disorders represent potentially debilitating conditions and can affect people of all ages. Such diseases may be acquired or congenital. Neurodevelopmental disorders represent a subset of disorders characterised by impairments of the growth and development of the brain or central nervous system. They are associated with widely varying degrees of difficulty which may have significant mental, emotional, physical, and economic consequences for individuals.
Acquired neurological diseases or disorders may be traumatic, that is, wherein an external force causes damage to the brain; or an injury resulting from, for example, infection, disease, toxicity, oxygen or glucose deprivation. A congenital neurological disorder typically exists at birth or before birth and may be the result of genetic abnormalities, the intrauterine environment, errors of morphogenesis, infection, or a chromosomal abnormality. Neurodevelopmental disorders may be acquired or congenital. Neurodevelopmental diseases or disorders in accordance with the present invention may include, for example, autism spectrum disorders.
Autism spectrum disorders (ASD) are a complex group of sporadic and familial developmental disorders affecting 1 in 150 births and characterized by abnormal social interaction, impaired communication, impaired social interaction, and restricted, repetitive patterns of behaviour, interests or activities. ASD includes autism Autistic Disorder, Asperger's Disorder, Childhood Disintegrative Disorder and Pervasive Developmental Disorder-Not Otherwise Specified (PDD-NOS) and Rett syndrome. The etiology of ASD is poorly understood and no single specific cause has been identified. However, certain risk factors are thought to contribute to the development of ASD, including genetics, prenatal and perinatal factors, neuroanatomical abnormalities, and environmental factors. For example, a genetic basis is evidenced by the greater than 70% concordance in monozygotic (MZ) twins and elevated risk in siblings compared to the population.
Autism spectrum disorders are highly variable neurodevelopmental disorders; distinguished not by a single symptom, but by a multitude of characteristic symptoms that typically first appear during infancy or childhood. Related symptoms may begin after the age of six months, becoming established around the age of two or three years, and continue through adulthood.
ASD is more common in males than females, with a ratio of approximately 5.5:1. Surprisingly, mutations in the only sex-linked ASD associated gene Neuroligin 3 are rare in ASD patients and no other sex-linked gene has so far been identified in ASD linkage or GWAS studies. However, the sexually dimorphic brain expressing CYP19A1 (encodes aromatase, the enzyme that synthesises oestrogens) gene is only 19 Mb away from a suggestive ASD linkage at 15q23-q25 7. Recently, it was reported that aromatase expression was lowered in ASD patients. Furthermore, it has been reported that CYP19A1 is a candidate gene for human cognitive functions implicated in reading, speech and language.
To date, there is no cure for ASD and a single, effective treatment has not been identified. Current treatments for autism spectrum disorders aim to increase quality of life and functional independence as well as reduce associated deficits and family distress. In certain cases, educational or behavioural therapies may improve functioning and decrease symptom severity. Outside of behavioural therapies, a number of different medications have been used, with varying degrees of success, to specifically reduce symptoms of ASD that interfere with social integration and function when behavioural treatments fail. Such medications include psychoactive drugs, anticonvulsants, antidepressants, stimulants, and antipsychotics. However, ASD patients often respond atypically to medications or the prescribed medications may have other adverse side effects. No single medication is known to relieve or reverse the core symptoms of ASD, such as social and communication impairments.
Accordingly, there is an on-going need to develop new therapeutic agents or methods of treating and/or preventing neurodevelopmental disorders such, as ASD.